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Biomedical subjects

C Zoccali

Publications and source records attributed to C Zoccali.

At least 19 recordsLinked to original sources
PubMed2006

Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol.

Endocannabinoids are a group of biologically active endogenous lipids that have recently emerged as important mediators in energy balance control. The two best studied endocannabinoids, anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the endogenous ligands of the central and peripheral cannabinoid receptors. Furthermore, AEA binds to the transient receptor potential vanilloid type-1 (TRPV1), a capsaicin-sensitive, non-selective cation channel. The synthesis of these endocannabinoids is catalyzed by the N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and the sn-1-selective diacylglycerol lipase (DAGL), whereas their degradation is accomplished by the fatty acid amide hydrolase (FAAH) and the monoglyceride lipase (MGL), respectively. We investigated the presence of a functional endocannabinoid system in human adipose tissue from seven healthy subjects. Subcutaneous abdominal adipose tissue underwent biochemical and molecular biology analyses, aimed at testing the expression of this system and its functional activity. AEA and 2-AG levels were detected and quantified by HPLC. Real time PCR analyzed the expression of the endocannabinoid system and immunofluorescence assays showed the distribution of its components in the adipose tissue. Furthermore, binding assay for the cannabinoid and vanilloid receptors and activity assay for each metabolic enzyme of the endocannabinoid system gave clear evidence of a fully operating system. The data presented herein show for the first time that the human adipose tissue is able to bind AEA and 2-AG and that it is endowed with the biochemical machinery to metabolize endocannabinoids.

Adipose Tissue↗
PubMed2006

ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease.

The rationale of this study is based on the fact that, both proteinuria and elevated asymmetric dimethyl arginine (ADMA) levels have been linked to the progression of vascular disease. Currently, there is not enough knowledge about any association between the levels of proteinuria and ADMA levels. Seventy-eight non-diabetic patients (42 men, 36 women, mean age of 26.1+/-5.2 years) with proteinuria having normal glomerular filtration rate were enrolled along with 38 healthy subjects (20 men, 18 women, mean age of 26.9+/-5.9 years). Proteinuria was below 3.5 g/day in 40 patients and above 3.5 g/day in 38 patients. Both groups had similar age, gender, and body mass index distributions. Serum ADMA, symmetric dimethyl arginine (SDMA), immunoreactive insulin, and high sensitivity C reactive protein (hsCRP) levels were measured. Insulin resistance was determined by homeostasis model assessment (HOMA). Serum ADMA, SDMA, insulin, hsCRP levels, and HOMA indexes were significantly higher in patients than in healthy control subjects. The above parameters were higher in the nephrotic range proteinuria group when compared to patients having protein levels below 3.5 g/day. There were significant correlations between the levels of proteinuria and the above parameters. According to the regression analysis, levels of proteinuria and hsCRP were significant determinants of serum ADMA levels. Our results indicate that, independent of other risk factors, ADMA is directly associated with proteinuria. Further studies are recommended to find out whether elevated ADMA levels are implicated in the high cardiovascular risk of proteinuric nephropathies.

Adult↗
PubMed2006

Low triiodothyronine and survival in end-stage renal disease.

Plasma triiodothyronine (fT3) is a strong predictor of adverse clinical outcomes in various clinical conditions. Since fT3 in patients with end-stage renal diseases (ESRD) is frequently reduced and is associated with inflammation and cardiovascular damage, we prospectively tested the hypothesis that it predicts death in a cohort of 200 hemodialysis patients. Plasma fT3 was lower in ESRD patients (P<0.001) than in healthy subjects and in clinically euthyroid patients with normal renal function. During the follow-up 102 patients died. Patients who died had significantly lower plasma fT3 than those who survived (P<0.001) and in a Kaplan-Meyer analysis plasma fT3 was associated with death (P<0.001). On multivariate Cox's regression analyses, adjusting for a series of traditional and emerging risk factors including inflammation markers, patients with relatively higher plasma fT3 (hazard ratio (HR) (1 pg/ml increase in fT3)) had a 50% reduction in the risk of death (HR=0.50, 95% CI: 0.35-0.72) as compared to those having relatively lower fT3 levels. Of note, plasma fT3 captured most of the predictive power of interleukin-6 (IL-6) because this latter variable emerged as a significant predictor of death only in a model excluding fT3. Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population.

Adult↗
PubMed2006

Traditional and emerging cardiovascular and renal risk factors: an epidemiologic perspective.

Patients with chronic kidney disease (CKD) represent an important segment of the population (7-10%) and, mostly because of the high risk of cardiovascular complications associated with renal insufficiency, detection and treatment of CKD is now a public health priority. Traditional risk factors can incite renal dysfunction and cardiovascular damage as well. As renal function deteriorates, non-traditional risk factors play an increasing role both in glomerular filtration rate (GFR) loss and cardiovascular damage. Secondary analyses of controlled clinical trials suggest that inflammation may be a modifiable risk factor both for cardiac ischemia and renal disease progression in patients with or at risk of coronary heart disease. Homocysteine predicts renal function loss in the general population and cardiovascular events in end-stage renal disease (ESRD), but evidence that this sulfur amino acid is directly implicated in the progression of renal disease and in the high cardiovascular mortality of uremic patients is still lacking. High sympathetic activity and raised plasma concentration of asymmetric dimethylarginine (ADMA) have been associated to reduced GFR in patients with CKD and to cardiovascular complications in those with ESRD but again we still lack clinical trials targeting these risk factors. Presently, the clinical management of CKD patients remains largely unsatisfactory because only a minority of these attain the treatment goals recommended by current guidelines. Thus, in addition to research into new and established risk factors, it is important that nephrologists make the best use of knowledge already available to optimize the follow-up of these patients.

Cardiovascular Diseases↗
PubMed2006

Homocysteine and risk in end-stage renal disease: a matter of context.

Like blood pressure and cholesterol, homocysteine shows a paradoxical inverse relationship with cardiovascular complications in end-stage renal disease (ESRD). A paper by Ducloux et al. in this issue adds perhaps decisive evidence on malnutrition-hypoalbuminemia as the main factor explaining the counterintuitive association between homocysteine and clinical outcome reported in previous studies.

Blood Pressure↗
PubMed2006

Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n=486; stage 4: n=430, stage 5: n=142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12-391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin-angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00-1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15-1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37-2.22 and odds ratio 2.85, 95% confidence interval 2.01-4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced CKD.

Aged↗
PubMed2006

Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal disease.

Urotensin II (UTN) is a vasoactive substance that may induce vasoconstriction or vasodilatation. Although this peptide is seen as a vasculotoxic substance, to date there is no prospective study examining the relationship between UTN and hard end points like cardiovascular (CV) events. UTN is much increased in end-stage renal disease (ESRD) and this disease may represent a useful natural model to explore the relationship between UTN and CV outcomes. In this study, we analysed the relationship between plasma UTN and incident CV events (fatal and non-fatal) in a cohort of 191 haemodialysis patients followed up for an average time of 3.6 years (range 0.07-5.8 years). Plasma UTN in haemodialysis patients (median: 6.5 ng/ml) was twice higher than in healthy subjects (median: 3.3 ng/ml). During the follow-up period, 94 patients died and 88 had incident fatal and non-fatal CV events. UTN was significantly lower in patients with incident CV events (median: 5.3 ng/ml) than in events-free patients (median: 7.1 ng/ml), and in a Kaplan-Meier analysis, high UTN was strongly and inversely associated with incident CV events (P<0.001). Multivariate Cox's regression analysis fully confirmed plasma UTN as an inverse predictor of adverse CV outcomes, and in this analysis, UTN resulted to be the third factor in rank, after age and diabetes, explaining the incidence of CV events. UTN is an inverse predictor of CV outcomes in ESRD. Our data suggest that UTN should not be necessarily seen as a vasculotoxic peptide in haemodialysis patients.

Age Factors↗
PubMed2006

A green light for troponin T in the cardiovascular risk stratification of continuous ambulatory peritoneal dialysis patients?

Troponin T is specifically qualified as a predictor of circulatory overload in peritoneal dialysis (PD) patients. Given the good standardization and the high reproducibility of the troponin T assay, this measurement may prove useful in the clinical management of PD patients. It still remains to be tested whether clinical policies incorporating troponin T may actually produce better outcomes in PD patients.

Biomarkers↗
PubMed2006

Asymmetric dimethylarginine in end-stage renal disease patients: a biomarker modifiable by calcium blockade and angiotensin II antagonism?

The nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk biomarker in cardiovascular and renal diseases. Apparently amlodipine and valsartan produce substantial reductions in the plasma concentration of this methylarginine in hemodialysis patients. These findings are of relevance for designing studies aimed at testing the etiologic relevance of ADMA to the high cardiovascular risk of ESRD.

Amlodipine↗
PubMed2003

Fibrinogen, inflammation and concentric left ventricular hypertrophy in chronic renal failure.

BACKGROUND: We investigated the relationship between fibrinogen and echocardiographic measurements of left ventricular (LV) geometry and LV function in a group of 192 patients with end stage renal disease (ESRD). RESULTS: Patients in the third fibrinogen tertile had higher mean wall thickness (MWT), relative wall thickness (RWT) and left ventricular mass index (LVMI) and lower LV end diastolic diameter and LV ejection fraction than those in the other tertiles. On multivariate analysis fibrinogen resulted to be an independent correlate of MWT (P = 0.001) and RWT (P = 0.0001) and the first factor in rank explaining the variance in LV ejection fraction (P = 0.0001). Left ventricular concentric hypertrophy was more prevalent (P = 0.001) in patients in the third fibrinogen tertile (n = 35, 54%) than in those in the second (n = 24, 37%) and first (n = 13, 21%) tertiles. In a multiple logistic regression model patients in the third tertile of fibrinogen had a risk for left ventricular concentric hypertrophy that was 3.56 (95% CI: 1.56-8.14) fold higher than in those in the first tertile (P = 0.003). CONCLUSIONS: Elevated fibrinogen is independently associated with LV concentric hypertrophy and systolic dysfunction in ESRD patients. These relationships may contribute to the negative prognostic impact of elevated fibrinogen levels in ESRD.

Blood Pressure↗
PubMed2003

Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure.

OBJECTIVE: Fibrinogen is an established predictor of cardiovascular events in the general population but the relationship between fibrinogen, mortality and incident cardiovascular complications has been very little investigated in patients with end-stage renal disease (ESRD). DESIGN AND SUBJECTS: We investigated the relationship between fibrinogen and all cause mortality and cardiovascular outcomes in a prospective cohort study in 192 patients on chronic haemodialysis treatment (follow-up: 34 +/- 16 months). RESULTS: Fibrinogen was significantly higher in patients who died during the follow-up than in those who survived. Similarly, fibrinogen was higher in patients who had fatal or nonfatal cardiovascular events than in event free patients. On multivariate Cox regression analysis fibrinogen was an independent predictor of survival [hazard ratio (1 g x L(-1) increase in plasma fibrinogen): 1.19, 95% confidence interval (CI): 1.05-1.35, P = 0.006] and a highly significant (P = 0.0008), independent predictor of fatal and nonfatal cardiovascular events [hazard ratio (1 g x L(-1) increase in plasma fibrinogen): 1.25, 95% CI: 1.10-1.43] in a model including traditional risk factors and serum C-reactive protein (CRP) and plasma homocysteine. CONCLUSIONS: Fibrinogen is as an independent risk factor for overall and cardiovascular mortality in patients with ESRD. Intervention studies are required to see whether reducing plasma fibrinogen may help to curb the exceedingly high cardiovascular risk of the uremic population.

Adult↗
PubMed2001

Urinary adrenomedullin is related to ET-1 and salt intake in patients with mild essential hypertension. Salt Sensitivity Group of Italian Society of Hypertension.

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However, there is no evidence that this substance is related to changes in salt intake in humans. In this study we sought whether the urinary excretion rate of this autacoid is related to salt intake and by the expected changes in arterial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind, randomized and crossover study comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day salt intake period. Twenty-four-hour ADM and endothelin-1 (ET-1) excretion rate were measured by radioimmunoassay on preextracted urinary samples (intraassay confidence variable <8%). The antibodies used in these assays had minimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria was measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01) as well as to changes in urinary ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excretion were related to those in urinary ET-1 (r = 0.26, P = .05), but were independent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, plasma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) for urinary ADM when urinary ET-1 was introduced into the model. In this model (multiple r = 0.31) urinary ET-1 resulted to be the only independent predictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. The data support the notion that these autacoids play a role in the regulation of sodium metabolism in patients with mild hypertension. The intercorrelations between ET-1, ADM, and microalbuminuria are compatible with the hypothesis that ET-1 is involved in a salt-induced increase in glomerular pressure and suggest that ADM may act as a counterregulatory factor in this situation.

Adrenomedullin↗
PubMed2001

Diagnostic potential of cardiac natriuretic peptides in dialysis patients.

BACKGROUND: In the general population, the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful to predict left ventricular hypertrophy (LVH) and LV systolic dysfunction. Whether these cardiac hormones have a similar diagnostic potential in dialysis patients is unknown. METHODS: We studied the diagnostic value of ANP and BNP for alterations in LV mass and function in a cohort of 246 dialysis patients without clinical evidence of heart failure. RESULTS: Both ANP and BNP were independently related to left ventricular mass (P < 0.0001) as well as to ejection fraction (P < 0.0001). In an analysis based on a prospectively defined threshold (95th percentile of the normal range), BNP had a significantly higher (P < 0.01) sensitivity (88%) than ANP (51%) for the diagnosis of LVH, but the positive predictive value of the two peptides was very similar (92 and 87%, respectively, P = NS). However, the negative predictive value of BNP for excluding LVH was 22% higher than that of ANP (53 vs. 31%, P = 0.05). Both natriuretic peptides had a high sensitivity for the detection of LV dysfunction (87 and 94%), but their positive predictive value was low (25 and 15%). Importantly, both ANP and BNP proved to be very useful for excluding this alteration (negative predictive value 97 and 96%, respectively). An analysis based on the "best cut-offs" of each peptide as identified on the basis of the ROC curves augmented the positive and negative prediction values of BNP for the diagnosis of LVH to 95 and 61%, respectively. This approach also raised the BNP-positive prediction value for the identification of LV dysfunction to 31% but did not modify the diagnostic potential of ANP (either for LVH or for LV dysfunction). CONCLUSIONS: Measuring the plasma concentration of cardiac natriuretic hormones, particularly BNP, may be useful for the identification of dialysis patients with LVH or for excluding systolic dysfunction.

Aged↗